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Fibroids, UterinePhase 1NCT02889848

Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) to Treat Uterine Leiomyoma (Fibroids)

A Phase 1 study testing Saline and EN3835 in people with Fibroids, Uterine and Leiomyoma, run by Advance Biofactures Corporation at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This pilot study evaluates the safety and tolerability of a single injection of collagenase enzyme directly into a uterine fibroid in subjects already selected for hysterectomy or myomectomy. Read more about this study

Who is it for?
Ages 35 to 50 years, women only
Conditions the study is for
Fibroids, Uterine, Leiomyoma
What is being tested?
Saline and EN3835
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
1 siteUnited States
Study dates
27 Oct 2016to 15 Nov 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Parous and non-parous women who have completed child-bearing (age criteria of > 35 years-old, and <50 years-old)
  • Currently practicing or willing to practice contraception throughout the duration of the study
  • Women with at least one or two fibroids greater than or equal to 3 cm diameter, and less than or equal to 10 cm diameter for subjects in Group 1, and at least one fibroid greater than or equal to 3 cm diameter, and less than or equal to 10 cm diameter for subjects in Group 2
  • Fibroids will be intramural fibroids which will be surrounded by a layer of myometrium. Fibroids must be well visualized on ultrasound examination and provide a clear path for injection
  • Women who were planning to undergo abdominal hysterectomy or myomectomy for treatment of symptomatic fibroids. Subjects must be willing to defer the operation until 24-96 hours after study treatment for Group 1 and for 60-90 days after study treatment for Group 2. The patients will understand that they may choose to have surgery or any other non-study treatment at any time after enrollment and end study participation
  • "Typical" large fibroids visualized as hypo-intense on a T2-weighted MRI scan

Who cannot join

  • Inability to understand study procedures or to comply with study visits and requirements
  • BMI > 40kg/m2
  • History of allergic reaction to study medication (Collagenase Clostridium Histolyticum) or any components of the study drug
  • Inability to undergo hysterectomy or myomectomy
  • Inability to tolerate MRI and transvaginal ultrasound procedures (i.e. presence of an intra-uterine device (IUD), pacemakers, aneurismal clips or other metallic devices that are not compatible with magnetic resonance imaging). However women with IUD's compatible with MRI are eligible for the study
  • Medical problems including: genetic diseases that cause fibroids, history of thromboembolic (blood clot) events or need for anticoagulation (Coumadin, Heparin, etc.) Subjects taking or planning to take anti-coagulant medication (except for ≤ 150 mg aspirin daily) within 7 days administration study drug and within 7 days before and after hysterectomy
Show all 19Show fewer
  • A history of cancer within the past 5 years
  • Abnormal liver function tests (typically, will be >20% elevation). Mild elevations will be at the discretion of the investigators, but undiagnosed liver conditions will represent an exclusion criterion
  • Pregnancy or lactation. Pregnancy will be evaluated by urine test every 30 days if necessary. Patients will be asked to use non-hormonal contraception methods while in this study
  • Severe anemia (hematocrit <30). Mild anemia is common in women with fibroids
  • Recent rapid growth of fibroids (i.e. doubling in size within one-six months period)
  • Any use of agents like Imidazoles, due to possible interference with metabolism
  • Unevaluated gynecologic abnormalities (unexplained vaginal bleeding, cervical dysplasia, or abnormal adnexal/ovarian mass)
  • Fibroids that are visualized on T2 and T1 weighted MRI as hyperdense or show cystic degeneration
  • Inability to undergo injection of fibroid with study drug for any reason, anatomic or other
  • Has a known systemic allergy to collagenase or any other excipient of EN3835 or any other procedural medication
  • Has, at any time, received collagenase as a treatment
  • Is planning to be treated with commercial XIAFLEX at any time during the study
  • Type 0 submucosal fibroids, submucosal fibroids with significant protrusion/ pedunculation and subserosal fibroids are not appropriate candidates for the injections

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21205

Other trials in United States

About this study

Official title: An Open Label, Dose Escalation Study to Assess Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) in Subjects With Uterine Leiomyoma (Fibroids)

This pilot study evaluates the safety and tolerability of a single injection of collagenase enzyme directly into a uterine fibroid in subjects already selected for hysterectomy or myomectomy.

Fibroids contain excessive amounts of collagen and it is possible that digestion of collagen may be beneficial in reducing pain and bleeding associated with fibroids.

Three subjects will be injected with saline only to evaluate the safety and effectiveness of the injection method. Additional subjects will then be injected with increasing doses of study drug.

Read the detailed description

Collagenase enzyme breaks down collagen and has shown efficacy in clinical trials for a number of diseases for which there is an accumulation of collagen.

It is possible that lysis of collagen may reduce the collagen content of fibroids thus decreasing the size of fibroids, and possibly reducing the stiffness of fibroids. This may result in reducing the symptoms of pain and bleeding associated with fibroids.

In this study three subjects will be injected with saline only followed immediately by hysterectomy in order to evaluate the safety and effectiveness of the injection method.

Twelve subjects will receive a single injection of study drug as follows: three subjects will receive a set dose of collagenase enzyme followed by hysterectomy or myomectomy 24-96 hours later (Group 1) to evaluate safety of the injection of study drug. Nine subjects will then receive increasing doses of collagenase enzyme followed by hysterectomy or myomectomy 60-90 days later (Group 2).

Being tested
Saline, EN3835
Medical subject headings
Leiomyoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SalineOther

    Saline injection

  • EN3835Drug

    Also called Collagenase clostridium histolyticum

    Comparison of maximum marketed dose and multiple doses EN3835

Study groups in NCT02889848
Study groupRoleWhat they receive
Saline onlySham comparatorInjection of saline to assess the injection procedure
Receives: Other: Saline
1.16 mg EN3835ExperimentalInjection of maximum marketed dose of EN3835 regardless of fibroid size
Receives: Drug: EN3835
Dose 1ExperimentalInjection of 0.05 mg EN3835 per cm3 fibroid
Receives: Drug: EN3835
Dose 2ExperimentalInjection of 0.1 mg EN3835 per cm3 fibroid
Receives: Drug: EN3835
Dose 3ExperimentalInjection of 0.2 mg EN3835 per cm3 fibroid
Receives: Drug: EN3835

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with treatment-related adverse events following a single injection of EN3835 into a fibroid

    Assessed by number of subjects with uterine injury or peritoneal irritation determined post hysterectomy

    Measured: Through hysterectomy or myomectomy (average = 60-90 days post injection)

Secondary outcomes (5)

  1. Change in symptoms of pain and bleeding and quality of life

    Determined by standardized questionnaires for menstrual distress, quality of life and sexual activity; McGill Pain Questionnaire

    Measured: Throughout the study prior to hysterectomy or myomectomy(avg 60-90 days post injection study drug)

  2. Reduction in size of treated fibroids- Group 2

    Size of fibroid to be determined post hysterectomy or myomectomy

    Measured: 60-90 days post injection study drug

  3. Increased rate of apoptosis of treated fibroids -Group 2

    Specimens to be taken post hysterectomy or myomectomy and evaluated by TUNEL staining

    Measured: 60-90 days post injection study drug

  4. Reduction in collagen content of treated fibroids-Group 2

    Specimens to be taken post hysterectomy or myomectomy and by tested histology stains

    Measured: 60-90 days post injection study drug

  5. Reduction in stiffness of treated fibroid-Group 2

    Specimens to be taken post hysterectomy or myomectomy and tested via rheometry

    Measured: 60-90 days post injection study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2016 (estimated)
  2. Study start27 Oct 2016
  3. Primary completion5 Oct 2018
  4. Study completion15 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02889848
Sponsor's protocol ID
FIB1154
Status last verified
Jun 2018
First submitted
22 Aug 2016
Last updated
10 Jul 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Islam MS, Afrin S, Singh B, Jayes FL, Brennan JT, Borahay MA, Leppert PC, Segars JH. Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids. Clin Transl Med. 2021 Jul;11(7):e475. doi: 10.1002/ctm2.475.

    PubMed 34323413

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Saline and EN3835 in people with Fibroids, Uterine and Leiomyoma, run by Advance Biofactures Corporation at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment-related adverse events following a single injection of EN3835 into a fibroid (time frame: Through hysterectomy or myomectomy (average = 60-90 days post injection)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02889848, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2019.

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